Design and Synthesis of Haptens for Kanamycins

Generating effective antibodies that achieve immune responses remains a challenging subject, which has long been the source of great interest both in the design of more efficient haptens for immunization and in the development of more direct synthetic methods. Kanamycin is one of aminoglycoside (AG) antibiotics widely applied in the treatment of animal diseases caused by Gram-positive and Gram-negative bacterial infections. Based on extensive expertise in antigen design, Creative Biolabs pays attention to the development of hapten synthetic strategies and provides one-stop, customized hapten design and synthesis services for kanamycin and its further use in antibody production.

Introduction to Kanamycin

Kanamycin, also referred to as kanamycin A, is a broad-spectrum antibiotic and its most commonly used format is kanamycin sulfate. The agent has been isolated from the bacterium Streptomyces kanamyceticus, a type of microorganisms frequently involved in the pathogenesis of infections in the clinic. Kanamycin functions by binding to the bacterial ribosome, thus inhibiting protein synthesis and leading to errors in the translation of genetic codes. There’re several components in the kanamycin complex, kanamycin A, B, C, and D. Kanamycin B is the 2-amino,2-deoxy-analog of kanamycin A. Kanamycin C is a minor component in the kanamycin complex, and a conjugate base of a kanamycin C(4+). Kanamycin D is a kanamycin derived from kanamycin A, in which the 3'-amino group is replaced by a hydroxy group. It is the conjugate acid of a kanamycin D(3+). Kanamycin A and C are isomers, while kanamycin B and D possess different functional groups. According to the structure-activity relationship study of AG antibiotics, the activity of this class of antibiotics is associated with the site of hydroxyl groups and amines as substituents on specific positions.

Fig.1 Chemical structure of kanamycin.

Rational Hapten Design Services at Creative Biolabs

Most pesticides, veterinary drugs, and small molecular compounds don’t have immunogenicity to generate antibodies because of lacking epitopes that can be recognized by T cells to elicit an immune response. As such, these small molecular targets are named hapten. Nevertheless, hapten can be chemically modified properly at a suitable location to introduce a spacer with an active group at the end, thereby the modified hapten is linked to a macromolecular carrier to form a hapten-carrier conjugate. The artificial hapten takes advantage of T cell epitopes to indirectly induce B cell to produce specific antibodies for small molecular compounds.

Recently, anti-hapten antibodies have been widely used for monitoring the titers of drugs and hormones in the body fluids of humans and animals. The preparation of the hapten immunogen affects the specificity of hapten-specific antiserum. Kanamycin exhibits strong antimicrobial activities against a diversity of aerobic bacteria. At Creative Biolabs, we’re specialized in hapten design and synthesis for small molecule compounds, especially kanamycin.

• Our Design & Synthesis Strategies

  There are a number of hapten design methods that can be provided by Creative Biolabs, including transition state analog (TSA) approach, reactive immunization, and many others. The basic requirement of hapten design is displayed as below:

  • To maintain the original structure of the hapten;
  • To make the hapten exposed on the surface of carriers as much as possible;

Therefore, after immunizing animals with artificial antigen, the hapten can be largely identified by the immune cells of experimental animals, evoking the immunity to generate a specific immune response and produce high specificity antibodies against this hapten. That is to say, the essential step of the hapten design is to determine the ideal modified sites on the hapten and to synthesize hapten derivative having a spacer arm in several-carbon-chain length with an active group.

• Our High Standard for Haptens

  According to recent studies, we have summarized a clear narrative about the design of optimized hapten derivatives, inducing but not limited to:

  1. A spacer arm in several-carbon-chain length attached to a carrier is preferred for hapten design;
  2. The active group at the end of the spacer should have no impacts on the electronic distribution of the hapten;
  3. The stereo-structure, electronic distribution, and hydrophobicity of hapten derivative ought to be similar to original hapten;
  4. After coupling happen with carrier proteins, the basic molecular structure of the hapten should be retained.

Advantages

• Advanced platforms and effective strategies for kanamycin hapten design and synthesis
• Expertise in structural properties and immunogenic analysis of small molecule compounds

Kanamycin is a bactericidal antibiotic of AGs, and has been applied to treat a variety of infections, available in oral and intravenous forms. The drug has a relatively narrow therapeutic index and could accumulate in the human body by food chains. it is necessary to develop a sensitive analytical method to detect kanamycin to ensure public health. Among them, the antigen-antibody reaction is a common and practical immunoassay. As a well-recognized antibody development expert, Creative Biolabs offers a series of custom services and optimized strategies to generate high-quality hapten and hapten-specific antibody products for global clients. If you’re interested in our services, please don’t hesitate to contact us or directly send us an inquiry.